A novel anti-cancer agent, FPDHP, induces anoikis ?in various human cancer cells through activation of calpain and downregulation of anoikis-related molecules
- Seon Goo Kim; Ji Hea Yooun; Dong Eun Kim; Eung‐Seok Lee; Taeg Kyu Kwon; Shin Kim; Jong Wook Park
- Dept. of Immunology (면역학); Institute for Medical Science (의과학연구소)
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- Resistance to anoikis and growth in anchorage-independent conditions are hallmarks of highly metastatic cancer cells. Anoikis is a type of apoptosis induced by inadequate cell/extracellular matrix (ECM) attachment and an attractive anti-cancer therapeutic strategy in cancer chemotherapeutic field. Therefore, the development of anoikis-inducing agents is useful and promising to overcome cancer. When FPDHP, a novel anoikis-inducing agent, was treated within 3 h, FPDHP induced massive cell detachment in various human cancer cells, irrespective of apoptosis. Moreover, FPDHP decreased the expression of integrins, FAK, focal adhesion signaling effectors (talin1 and talin2), tight junction proteins (ZO-1, ZO-2, and ZO-3), transcriptional mediators of epithelial-mesenchymal transition (EMT) (Snail1 and Snail2), and anoikis-related protein, such as Mcl-1 (L). Interestingly, Caki/ZO-2 and Caki/α6 are significantly suppressed the FPDHP-mediated cell detachment, and the constitutive active form of Akt and overexpression of Mcl-1 (L) partially inhibited the cellular detachment induced by FPDHP. On the other hand, when FPDHP was treated for more than 12 h, FPDHP induced caspase-dependent apoptosis and release of AIF and cytochrome c from mitochondria. Furthermore, FPDHP down regulated Mcl-1 (L) at post-transcriptional level, and overexpression of Mcl-1 (L) partially attenuated the apoptosis induced by FPDHP. Additionally, PD150606, a calpain inhibitor, attenuated FPDHP-mediated cell detachment and apoptosis. Taken together, these results suggest that FPDHP possesses anoikis-inducing activity or potential making cancer cells susceptible to anoikis, and may be developed as a novel active compound for cancer treatment.
- FAK; FPDHP; MCl-1 (L); anoikis; apoptosis; calpain
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- 1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
- Keimyung Author(s)
- 김신; 권택규; 박종욱
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